Novel ANKRD17 variants implicate synaptic and mitochondrial disruptions in intellectual disability and autism spectrum disorder / Dan XIA in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Novel ANKRD17 variants implicate synaptic and mitochondrial disruptions in intellectual disability and autism spectrum disorder Type de document : texte imprimé Auteurs : Dan XIA, Auteur ; Yuanyuan XU, Auteur ; Zhanwen HE, Auteur ; Rui CHEN, Auteur ; Xiaoqin XIAO, Auteur ; Xiaojuan LI, Auteur ; Kewen DENG, Auteur ; Shuyun DENG, Auteur ; Lina ZHANG, Auteur ; Jieming ZHANG, Auteur ; Xiaofang PENG, Auteur ; Zhe MENG, Auteur ; Ruohao WU, Auteur ; Dilong WANG, Auteur ; Zulin LIU, Auteur ; Hui CHEN, Auteur ; Lu LI, Auteur ; Liyang LIANG, Auteur Langues : Anglais (eng) Mots-clés : Child  Humans  Male  Autism Spectrum Disorder/genetics  Intellectual Disability/genetics  Mitochondria/genetics/metabolism  Synapses  ANKRD17 haploinsufficiency  Autism Spectrum Disorder (ASD)  Intellectual Disability (ID)  Mitochondrial inhibition  Synaptic protein abnormalities  reviewed and approved by the Ethics Committee of Sun Yat-sen Memorial Hospital of  Sun Yat-sen University (Ethical code: SYSEC-KY-KS-2023–153 and BAP20230154).  Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : ANKRD17 has recently been implicated in intellectual disability (ID) and autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. Using trio whole-exome sequencing (Trio-WES) and chromosomal microarray analysis (CMA), we identified two unrelated cases with novel de novo heterozygous ANKRD17 variants. Case 1 describes a fetus with multiple congenital anomalies, where genetic analysis revealed a microdeletion at 4q13.3 truncating the ANKRD17 gene. Case 2 involves a 12-year-old male presenting with mild ID and progressive social impairments, associated with a NM_032217.5: c.1252 C > T (p.Arg418*) variation in ANKRD17. Our study highlighted in mouse models an association between Ankrd17 haploinsufficiency and deficits in social behavior, spatial learning and memory, as well as elevated anxiety. Furthermore, our studies suggest dysregulation of synaptic proteins and mitochondrial function, along with impaired neural circuits following Ankrd17 knockdown. These results expand the genetic and phenotypic spectrum of ANKRD17-related disorders, underscore the critical role of mitochondrial dysfunction in the pathophysiology of ANKRD17-related ID and ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09619-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Novel ANKRD17 variants implicate synaptic and mitochondrial disruptions in intellectual disability and autism spectrum disorder [texte imprimé] / Dan XIA, Auteur ; Yuanyuan XU, Auteur ; Zhanwen HE, Auteur ; Rui CHEN, Auteur ; Xiaoqin XIAO, Auteur ; Xiaojuan LI, Auteur ; Kewen DENG, Auteur ; Shuyun DENG, Auteur ; Lina ZHANG, Auteur ; Jieming ZHANG, Auteur ; Xiaofang PENG, Auteur ; Zhe MENG, Auteur ; Ruohao WU, Auteur ; Dilong WANG, Auteur ; Zulin LIU, Auteur ; Hui CHEN, Auteur ; Lu LI, Auteur ; Liyang LIANG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Child  Humans  Male  Autism Spectrum Disorder/genetics  Intellectual Disability/genetics  Mitochondria/genetics/metabolism  Synapses  ANKRD17 haploinsufficiency  Autism Spectrum Disorder (ASD)  Intellectual Disability (ID)  Mitochondrial inhibition  Synaptic protein abnormalities  reviewed and approved by the Ethics Committee of Sun Yat-sen Memorial Hospital of  Sun Yat-sen University (Ethical code: SYSEC-KY-KS-2023–153 and BAP20230154).  Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : ANKRD17 has recently been implicated in intellectual disability (ID) and autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. Using trio whole-exome sequencing (Trio-WES) and chromosomal microarray analysis (CMA), we identified two unrelated cases with novel de novo heterozygous ANKRD17 variants. Case 1 describes a fetus with multiple congenital anomalies, where genetic analysis revealed a microdeletion at 4q13.3 truncating the ANKRD17 gene. Case 2 involves a 12-year-old male presenting with mild ID and progressive social impairments, associated with a NM_032217.5: c.1252 C > T (p.Arg418*) variation in ANKRD17. Our study highlighted in mouse models an association between Ankrd17 haploinsufficiency and deficits in social behavior, spatial learning and memory, as well as elevated anxiety. Furthermore, our studies suggest dysregulation of synaptic proteins and mitochondrial function, along with impaired neural circuits following Ankrd17 knockdown. These results expand the genetic and phenotypic spectrum of ANKRD17-related disorders, underscore the critical role of mitochondrial dysfunction in the pathophysiology of ANKRD17-related ID and ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09619-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

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